tbuckley/cabot-search huggingface dataset:
Corrigendum to “Comparative efficacy of omega-3 polyunsaturated fatty acids on major cardiovascular events: A network meta-analysis of randomized controlled trials” [Progress in Lipid Research. 2022 Oct 28;88:101196. doi: 10.1016/j.plipres.2022.101196]
Authors: Bo Yang, Ping-Tao Tseng, Xiang Hu, Bing-Yan Zeng, Jane Pei-Chen Chang, Yang Liu, Wei-Jie Chu, Shuang-Shuang Zhang, Zhi-Liang Zhou, Chih-Sheng Chu, Cheng-Ho Chang, Yu-Kang Tu, Yi-Cheng Wu, Brendon Stubbs, Andre F Carvalho, Pao-Yen Lin, Yutaka J Matsuoka, Mein-Woei Suen, Kuan-Pin Su
Journal: Progress in Lipid Research (2022)
Cardiac xenotransplantation: from concept to clinic
Authors: Bruno Reichart, David K C Cooper, Matthias Längin, Ralf R Tönjes, Richard N Pierson, Eckhard Wolf
Journal: Cardiovascular Research (2022)

Abstract For many patients with terminal/advanced cardiac failure, heart transplantation is the most effective, durable treatment option, and offers the best prospects for a high quality of life. The number of potentially life-saving donated human organs is far fewer than the population who could benefit from a new heart, resulting in increasing numbers of patients awaiting replacement of their failing heart, high waitlist mortality, and frequent reliance on interim mechanical support for many of those deemed among the best candidates but who are deteriorating as they wait. Currently, mechanical assist devices supporting left ventricular or biventricular heart function are the only alternative to heart transplant that is in clinical use. Unfortunately, the complication rate with mechanical assistance remains high despite advances in device design and patient selection and management, and the quality of life of the patients even with good outcomes is only moderately improved. Cardiac xenotransplantation from genetically multi-modified (GM) organ-source pigs is an emerging new option as demonstrated by the consistent long-term success of heterotopic (non-life-supporting) abdominal and life-supporting orthotopic porcine heart transplantation in baboons, and by a recent ‘compassionate use’ transplant of the heart from a GM pig with 10 modifications into a terminally ill patient who survived for 2 months. In this review, we discuss pig heart xenotransplantation as a concept, including pathobiological aspects related to immune rejection, coagulation dysregulation, and detrimental overgrowth of the heart, as well as GM strategies in pigs to prevent or minimize these problems. Additional topics discussed include relevant results of heterotopic and orthotopic heart transplantation experiments in the pig-to-baboon model, microbiological and virologic safety concepts, and efficacy requirements for initiating formal clinical trials. An adequate regulatory and ethical framework as well as stringent criteria for the selection of patients will be critical for the safe clinical development of cardiac xenotransplantation, which we expect will be clinically tested during the next few years.
A case of rectal diverticulitis resembling a submucosal tumor under colorectal endoscopy: a hitherto undescribed lesion
Authors: Yan Ou, Long Chen, Yan Ye, Ruiqiang Yang, Yankun Song, Xianjing Yu, Juan Liao
Journal: Endoscopy (2022)

A 47-year-old man was referred to our hospital for a routine colorectal endoscopy health check-up. During the endoscopy, a submucosal tumor (SMT)-like lesion with a smooth mucosal surface, approximately 10 mm in diameter and with a top pinhole-like opening with overflowing yellow-white liquid, was found in the rectum ([Fig. 1]). Endoscopic ultrasonography revealed that the SMT tumor located in the third layer was a single cystic lesion ([Fig. 2]). The patient presented with no symptoms of abdominal pain, fever, or mucus bloody stool. Laboratory profiles were all within normal limits. An enhanced abdominal computed tomography revealed a nodule lesion in the rectum with a slight enhancement. Enlargement of the regional lymph node was not observed. The lesion was clinically diagnosed as a rectal cystic tumor with a possibility of a benign tumor. Therefore, endoscopic submucosal dissection ([Fig. 3]) was performed after patient consent was obtained. We successfully performed an en bloc resection of the lesion ([Fig. 4]).
Symptomatic cholelithiasis and acute cholecystitis treated by EUS-guided gallbladder drainage with gallbladder toilette
Authors: Benedetto Mangiavillano, Federica Calabrese, Francesco Auriemma, Danilo Paduano, Alessandro De Marco, Alessandro Repici
Journal: Endoscopy (2022)

An 81-year-old woman with a history of colorectal cancer, connective tissue disease, previous dorsal spine stabilization, and late mild cognitive impairment was admitted to our emergency department with abdominal pain, fever, and jaundice. She had experienced recurrent upper right abdominal pain for the past 2 years and had been diagnosed with cholelithiasis. Laboratory findings showed leukocytosis, elevated C-reactive protein levels, elevated alkaline phosphatase, and hyperbilirubinemia. A computed tomography (CT) scan revealed gallbladder distention and wall thickening with pericholecystic fluid and a 25-mm gallstone impacted in the infundibulum.
Reanalysis of Trichloroethylene and Tetrachloroethylene Metabolism to Glutathione Conjugates Using Human, Rat, and Mouse Liver <i>in Vitro</i> Models to Improve Precision in Risk Characterization
Authors: Alan Valdiviezo, Grace E. Brown, Ashlin R. Michell, Cristiana M. Trinconi, Vedant V. Bodke, Salman R. Khetani, Yu-Syuan Luo, Weihsueh A. Chiu, Ivan Rusyn
Journal: Environmental Health Perspectives (2022)

Background: Both trichloroethylene (TCE) and tetrachloroethylene (PCE) are high-priority chemicals subject to numerous human health risk evaluations by a range of agencies. Metabolism of TCE and PCE determines their ultimate toxicity; important uncertainties exist in quantitative characterization of metabolism to genotoxic moieties through glutathione (GSH) conjugation and species differences therein. Objectives: This study aimed to address these uncertainties using novel in vitro liver models, interspecies comparison, and a sensitive assay for quantification of GSH conjugates of TCE and PCE, S-(1,2-dichlorovinyl)glutathione (DCVG) and S-(1,2,2-trichlorovinyl) glutathione (TCVG), respectively. Methods: Liver in vitro models used herein were suspension, 2-D culture, and micropatterned coculture (MPCC) with primary human, rat, and mouse hepatocytes, as well as human induced pluripotent stem cell (iPSC)-derived hepatocytes (iHep). Results: We found that, although efficiency of metabolism varied among models, consistent with known differences in their metabolic capacity, formation rates of DCVG and TCVG generally followed the patterns human≥rat≥mouse, and primary hepatocytes>iHep. Data derived from MPCC were most consistent with estimates from physiologically based pharmacokinetic models calibrated to in vivo data. Discussion: For TCE, the new data provided additional empirical support for inclusion of GSH conjugation-mediated kidney effects as critical for the derivation of noncancer toxicity values. For PCE, the data reduced previous uncertainties regarding the extent of TCVG formation in humans; this information was used to update several candidate kidney-specific noncancer toxicity values. Overall, MPCC-derived data provided physiologically relevant estimates of GSH-mediated metabolism of TCE and PCE to reduce uncertainties in interspecies extrapolation that constrained previous risk evaluations, thereby increasing the precision of risk characterizations of these high-priority toxicants. https://doi.org/10.1289/EHP12006
Expert consensus on regenerative endodontic procedures
Authors: Xi Wei, Maobin Yang, Lin Yue, Dingming Huang, Xuedong Zhou, Xiaoyan Wang, Qi Zhang, Lihong Qiu, Zhengwei Huang, Hanguo Wang, Liuyan Meng, Hong Li, Wenxia Chen, Xiaoying Zou, Junqi Ling
Journal: International Journal of Oral Science (2022)

Abstract Regenerative endodontic procedures (REPs) is a biologic-based treatment modality for immature permanent teeth diagnosed with pulp necrosis. The ultimate objective of REPs is to regenerate the pulp-dentin complex, extend the tooth longevity and restore the normal function. Scientific evidence has demonstrated the efficacy of REPs in promotion of root development through case reports, case series, cohort studies, and randomized controlled studies. However, variations in clinical protocols for REPs exist due to the empirical nature of the original protocols and rapid advancements in the research field of regenerative endodontics. The heterogeneity in protocols may cause confusion among dental practitioners, thus guidelines and considerations of REPs should be explicated. This expert consensus mainly discusses the biological foundation, the available clinical protocols and current status of REPs in treating immature teeth with pulp necrosis, as well as the main complications of this treatment, aiming at refining the clinical management of REPs in accordance with the progress of basic researches and clinical studies, suggesting REPs may become a more consistently evidence-based option in dental treatment.
Multiomic analysis for optimization of combined focal and immunotherapy protocols in murine pancreatic cancer
Authors: James Wang, Brett Z. Fite, Aris J. Kare, Bo Wu, Marina Raie, Spencer K. Tumbale, Nisi Zhang, Ryan R. Davis, Clifford G. Tepper, Sharon Aviran, Aaron M. Newman, Daniel A. King, Katherine W. Ferrara
Journal: Theranostics (2022)

Background: Although combination immunotherapies incorporating local and systemic components have shown promising results in treating solid tumors, varied tumor microenvironments (TMEs) can impact immunotherapeutic efficacy. Method: We designed and evaluated treatment strategies for breast and pancreatic cancer combining magnetic resonance-guided focused ultrasound (MRgFUS) ablation and antibody therapies. With a combination of single-cell sequencing, spectral flow cytometry, and histological analyses, we profiled an immune-suppressed KPC (Kras+/LSL-G12D; Trp53+/LSL-R172H; Pdx1-Cre) pancreatic adenocarcinoma (MT4) model and a dense epithelial neu deletion (NDL) HER2+ mammary adenocarcinoma model with a greater fraction of lymphocytes, natural killer cells and activated dendritic cells. We then performed gene ontology analysis, spectral and digital cytometry to assess the immune response to combination immunotherapies and correlation with survival studies. Result: Based on gene ontology analysis, adding ablation to immunotherapy enriched immune cell migration pathways in the pancreatic cancer model and extensively enriched wound healing pathways in the breast cancer model. With CIBERSORTx digital cytometry, aCD40 + aPD-1 immunotherapy combinations enhanced dendritic cell activation in both models. In the MT4 TME, adding the combination of aCD40 antibody and checkpoint inhibitors (aPD-1 and aCTLA-4) with ablation was synergistic, increasing activated natural killer cells and T cells in distant tumors. Furthermore, ablation with immunotherapy upregulated critical Ly6c myeloid remodeling phenotypes that enhance T-cell effector function and increased granzyme and protease encoding genes by as much as 100-fold. Ablation combined with immunotherapy then extended survival in the MT4 model to a greater extent than immunotherapy alone. Conclusion: In summary, TME profiling informed a successful multicomponent treatment protocol incorporating ablation and facilitated differentiation of TMEs in which ablation is most effective.
Anti-adhesive bioresorbable elastomer-coated composite hernia mesh that reduce intraperitoneal adhesions
Authors: Shantanu P. Nikam, Yen-Hao Hsu, Jessica R. Marks, Catalin Mateas, Natasha C. Brigham, Samantha M. McDonald, Dana S. Guggenheim, David Ruppert, Jeffrey I. Everitt, Howard Levinson, Matthew L. Becker
Journal: Biomaterials (2022)
Risk Stratification for Sarcopenic Obesity in Subjects With Nonalcoholic Fatty Liver Disease
Authors: Ho Soo Chun, Minjong Lee, Hye Ah Lee, Sejin Lee, Soyeon Kim, Ye Jun Jung, Chaewon Lee, Hyoeun Kim, Han Ah Lee, Hwi Young Kim, Kwon Yoo, Tae Hun Kim, Sang Hoon Ahn, Seung Up Kim
Journal: Clinical Gastroenterology and Hepatology (2022)
Vision protection and robust axon regeneration in glaucoma models by membrane-associated Trk receptors
Authors: Euido Nishijima, Sari Honda, Yuta Kitamura, Kazuhiko Namekata, Atsuko Kimura, Xiaoli Guo, Yuriko Azuchi, Chikako Harada, Akira Murakami, Akira Matsuda, Tadashi Nakano, Luis F. Parada, Takayuki Harada
Journal: Molecular Therapy (2022)

Activation of neurotrophic factor signaling is a promising therapy for neurodegeneration. However, the transient nature of ligand-dependent activation limits its effectiveness. In this study, we solved this problem by inventing a system that forces membrane localization of the intracellular domain of tropomyosin receptor kinase B (iTrkB), which results in constitutive activation without ligands. Our system overcomes the small size limitation of the genome packaging in adeno-associated virus (AAV) and allows high expression of the transgene. Using AAV-mediated gene therapy in the eyes, we demonstrate that iTrkB expression enhances neuroprotection in mouse models of glaucoma and stimulates robust axon regeneration after optic nerve injury. In addition, iTrkB expression in the retina was also effective in an optic tract transection model, in which the injury site is near the superior colliculus. Regenerating axons successfully formed pathways to their brain targets, resulting in partial recovery of visual behavior. Our system may also be applicable to other trophic factor signaling pathways and lead to a significant advance in the field of gene therapy for neurotrauma and neurodegenerative disorders, including glaucoma.
Intravenous immunoglobulins, cyclosporine, and best supportive care in epidermal necrolysis: Diverse effects on systemic inflammation
Authors: Veronika Schmidt, Sophie Lalevée, Stephan Traidl, Milad Ameri, Reihane Ziadlou, Saskia Ingen‐Housz‐Oro, Caroline Barau, Nicolas de Prost, Mirjam Nägeli, Yasutaka Mitamura, Barbara Meier‐Schiesser, Alexander A. Navarini, Lars E. French, Emmanuel Contassot, Marie‐Charlotte Brüggen
Journal: Allergy (2022)

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but potentially life-threatening cutaneous adverse reactions. There is still no consensus on adjuvant treatments, and little is known about their effects on systemic inflammation in SJS/TEN. Our aim was to characterize the systemic and cutaneous immune profiles of SJS/TEN patients and to investigate whether/how intravenous immunoglobulins (IVIG), cyclosporine A (CSA), and best supportive care only (BSCO) affected the systemic immune signature and clinical outcome (6 week-mortality, complications, hospitalization stay).We included 16 patients with SJS/TEN, treated with high-dose IVIG (n = 8), CSA (n = 4) or BSCO (n = 4). Serial serum samples were obtained prior-, 5-7 days, and 21 days after treatment onset. Serum levels of inflammation-/immune response-associated proteins were measured by high-throughput proteomics assay (OLINK) and cytotoxic molecules by ELISA. RNA extracted from skin biopsies collected prior treatment was analyzed by Nanostring.Serum inflammatory profiles in SJS/TEN patients were notably characterized by massive upregulation of type 1 immune response and proinflammatory markers. Surprisingly, there was limited overlap between cutaneous and serum immune profiles. Serial serological measurements of immune response markers showed very diverse dynamics between the different treatment groups. IVIG-treated patients showed completely different dynamics and most significant proteomic changes in an early phase (Day 5-7). In all treatment groups, type 1-/inflammatory response markers were dampened at day 21. Clinically, there were no outcome differences.Our study demonstrates that BSCO, CSA, and IVIG have very diverse biological effects on the systemic inflammatory response in SJS/TEN, which may not correlate with clinical outcome differences.
Sounding the alarmins—The role of alarmin cytokines in asthma
Authors: Gail M. Gauvreau, Celine Bergeron, Louis‐Philippe Boulet, Donald W. Cockcroft, Andréanne Côté, Beth E. Davis, Richard Leigh, Irvin Myers, Paul M. O'Byrne, Roma Sehmi
Journal: Allergy (2022)

The alarmin cytokines thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25 are epithelial cell-derived mediators that contribute to the pathobiology and pathophysiology of asthma. Released from airway epithelial cells exposed to environmental triggers, the alarmins drive airway inflammation through the release of predominantly T2 cytokines from multiple effector cells. The upstream positioning of the alarmins is an attractive pharmacological target to block multiple T2 pathways important in asthma. Blocking the function of TSLP inhibits allergen-induced responses including bronchoconstriction, airway hyperresponsiveness, and inflammation, and subsequent clinical trials of an anti-TSLP monoclonal antibody, tezepelumab, in asthma patients demonstrated improvements in lung function, airway responsiveness, inflammation, and importantly, a reduction in the rate of exacerbations. Notably, these improvements were observed in patients with T2-high and with T2-low asthma. Clinical trials blocking IL-33 and its receptor ST2 have also shown improvements in lung function and exacerbation rates; however, the impact of blocking the IL-33/ST2 axis in T2-high versus T2-low asthma is unclear. To date, there is no evidence that IL-25 blockade is beneficial in asthma. Despite the considerable overlap in the cellular functions of IL-25, IL-33, and TSLP, they appear to have distinct roles in the immunopathology of asthma.
Machine Learning for Lung Cancer Diagnosis, Treatment, and Prognosis
Authors: Yawei Li, Xin Wu, Ping Yang, Guoqian Jiang, Yuan Luo
Journal: Genomics Proteomics & Bioinformatics (2022)

The recent development of imaging and sequencing technologies enables systematic advances in the clinical study of lung cancer. Meanwhile, the human mind is limited in effectively handling and fully utilizing the accumulation of such enormous amounts of data. Machine learning-based approaches play a critical role in integrating and analyzing these large and complex datasets, which have extensively characterized lung cancer through the use of different perspectives from these accrued data. In this article, we provide an overview of machine learning-based approaches that strengthen the varying aspects of lung cancer diagnosis and therapy, including early detection, auxiliary diagnosis, prognosis prediction, and immunotherapy practice. Moreover, we highlight the challenges and opportunities for future applications of machine learning in lung cancer.
Lymph node lymphatic endothelial cells as multifaceted gatekeepers in the immune system
Authors: Akira Takeda, Marko Salmi, Sirpa Jalkanen
Journal: Trends in Immunology (2022)

Single-cell technologies have recently allowed the identification of multiple lymphatic endothelial cell (LEC) subsets in subcapsular, paracortical, medullary, and other lymph node (LN) sinus systems in mice and humans. New analyses show that LECs serve key immunological functions in the LN stroma during immune responses. We discuss the roles of different LEC types in guiding leukocyte and cancer cell trafficking to and from the LN parenchyma, in capturing microbes, and in transporting, presenting, and storing lymph-borne antigens in distinct types of lymphatic sinuses. We underscore specific adaptations of human LECs and raise unanswered questions concerning LEC functions in human disease. Despite our limited understanding of human lymphatics – hampering clinical translation in inflammation and metastasis – we support the potential of LN LECs as putative targets for boosting/inhibiting immunoreactivity.
B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing
Authors: Annika Frede, Paulo Czarnewski, Gustavo Monasterio, Kumar P. Tripathi, David A. Bejarano, Ricardo O. Ramirez Flores, Chiara Sorini, Ludvig Larsson, Xinxin Luo, Laura Geerlings, Claudio Novella-Rausell, Chiara Zagami, Raoul Kuiper, Rodrigo A. Morales, Francisca Castillo, Matthew Hunt, Livia Lacerda Mariano, Yue O.O. Hu, Camilla Engblom, Ana-Maria Lennon-Duménil, Romy Mittenzwei, Astrid M. Westendorf, Nadine Hövelmeyer, Joakim Lundeberg, Julio Saez-Rodriguez, Andreas Schlitzer, Srustidhar Das, Eduardo J. Villablanca
Journal: Immunity (2022)

Therapeutic promotion of intestinal regeneration holds great promise, but defining the cellular mechanisms that influence tissue regeneration remains an unmet challenge. To gain insight into the process of mucosal healing, we longitudinally examined the immune cell composition during intestinal damage and regeneration. B cells were the dominant cell type in the healing colon, and single-cell RNA sequencing (scRNA-seq) revealed expansion of an IFN-induced B cell subset during experimental mucosal healing that predominantly located in damaged areas and associated with colitis severity. B cell depletion accelerated recovery upon injury, decreased epithelial ulceration, and enhanced gene expression programs associated with tissue remodeling. scRNA-seq from the epithelial and stromal compartments combined with spatial transcriptomics and multiplex immunostaining showed that B cells decreased interactions between stromal and epithelial cells during mucosal healing. Activated B cells disrupted the epithelial-stromal cross talk required for organoid survival. Thus, B cell expansion during injury impairs epithelial-stromal cell interactions required for mucosal healing, with implications for the treatment of IBD.
Decreased propionyl-CoA metabolism facilitates metabolic reprogramming and promotes hepatocellular carcinoma
Authors: Jiaqi Sun, Jun Ding, Qingsong Shen, Xiyang Wang, Min Wang, Yongping Huang, Xuechun Zhang, Huan Zhu, Feng Zhang, Dongde Wu, Min Peng, Zhonglin Zhang, Yufeng Yuan, Wenhua Li, Zhi-Gang She, Xiao-Jing Zhang, Hongliang Li, Peng Zhang, Zan Huang
Journal: Journal of Hepatology (2022)
Mucosal-associated invariant T cells for cancer immunotherapy
Authors: Yan-Ruide Li, Kuangyi Zhou, Matthew Wilson, Adam Kramer, Yichen Zhu, Niels Dawson, Lili Yang
Journal: Molecular Therapy (2022)

Human mucosal-associated invariant T (MAIT) cells are characterized by their expression of an invariant TCR α chain Vα7.2-Jα33/Jα20/Jα12 paired with a restricted TCR β chain. MAIT cells recognize microbial peptides presented by the highly conserved MHC class I-like molecule MR1 and bridge the innate and acquired immune systems to mediate augmented immune responses. Upon activation, MAIT cells rapidly proliferate, produce a variety of cytokines and cytotoxic molecules, and trigger efficient antitumor immunity. Administration of a representative MAIT cell ligand 5-OP-RU effectively activates MAIT cells and enhances their antitumor capacity. In this review, we introduce MAIT cell biology and their importance in antitumor immunity, summarize the current development of peripheral blood mononuclear cell-derived and stem cell-derived MAIT cell products for cancer treatment, and discuss the potential of genetic engineering of MAIT cells for off-the-shelf cancer immunotherapy.